The effect of inhibitors of arachidonic acid metabolism on drug-induced contractions in isolated tracheal smooth muscle of the pig.
1 The regulation of drug-induced tone in airways smooth muscle was examined in an isolated preparation of swine tracheal smooth muscle. 2 The trachea contracted (isometric) to histamine, 2-pyridylethylamine (2-PEA), acetylcholine and K+ but no response to histamine H2-receptor agonists were observed. 3 Histamine-induced contractions (100 microM) were potentiated by 213.3% by indomethacin (1 microM) and by 126.9% by sodium salicylate (250 microM). These inhibitors had only slight or no effects on acetylcholine-induced tone. 2-PEA responses were also potentiated by indomethacin but there were no changes in the response to H2-receptor agonists in the presence of indomethacin. The indomethacin-mediated potentiation of histamine was blocked by 5, 8, 11, 14-eicosatetraynoic acid (10 microM). FPL 55712 had no effect on these responses. 4 Mepacrine (100 microM) inhibited responses to histamine but not those to acetylcholine. No effect was observed with dexamethasone (up to 100 microM). 5 Prostaglandin E2 caused relaxation but arachidonic acid did not. 6 The possibility that histamine H1-agonist-induced contractions are regulated by contractile products of the arachidonic acid lipoxygenase pathway is discussed.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects; D012980:Sodium Salicylate / Q000494:pharmacology; D013552:Swine; D014132:Trachea / Q000187:drug effects
D001095:Arachidonic Acids; D011458:Prostaglandins E; D011968:Receptors, Histamine; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D003907:Dexamethasone; D011796:Quinacrine; D000109:Acetylcholine; D011188:Potassium; D012980:Sodium Salicylate; D007213:Indomethacin